Laser interstitial thermal therapy of the spine: technical aspects.

Spinal laser interstitial thermal therapy has been developed as a minimally invasive modality to treat epidural spinal tumors percutaneously. The safe and effective use of this technology requires meticulous preoperative trajectory planning and an intraoperative workflow incorporating navigation and MR thermography. Instrumented stabilization can be performed during the same operation if needed. Operative considerations and technical aspects are reviewed. The video can be found here: https://youtu.be/P--frsag6gU .

The Role of Extent of Resection in IDH1 Wild-Type or Mutant Low-Grade Gliomas.

BACKGROUND: Maximizing extent of resection (EOR) improves outcomes in adults with World Health Organization (WHO) grade II low-grade gliomas (LGG). However, recent studies demonstrate that LGGs bearing a mutation in the isocitrate dehydrogenase 1 (IDH1) gene are a distinct molecular and clinical entity. It remains unclear whether maximizing EOR confers an equivalent clinical benefit in IDH mutated (mtIDH) and IDH wild-type (wtIDH) LGGs. OBJECTIVE: To assess the impact of EOR on malignant progression-free survival (MPFS) and overall survival (OS) in mtIDH and wtIDH LGGs. METHODS: We performed a retrospective review of 74 patients with WHO grade II gliomas and known IDH mutational status undergoing resection at a single institution. EOR was assessed with quantitative 3-dimensional volumetric analysis. The effect of predictor variables on MPFS and OS was analyzed with Cox regression models and the Kaplan-Meier method. RESULTS: Fifty-two (70%) mtIDH patients and 22 (30%) wtIDH patients were included. Median preoperative tumor volume was 37.4 cm3; median EOR of 57.6% was achieved. Univariate Cox regression analysis confirmed EOR as a prognostic factor for the entire cohort. However, stratifying by IDH status demonstrates that greater EOR independently prolonged MPFS and OS for wtIDH patients (hazard ratio [HR] = 0.002 [95% confidence interval {CI} 0.000-0.074] and HR = 0.001 [95% CI 0.00-0.108], respectively), but not for mtIDH patients (HR = 0.84 [95% CI 0.17-4.13] and HR = 2.99 [95% CI 0.15-61.66], respectively). CONCLUSION: Increasing EOR confers oncologic and survival benefits in IDH1 wtLGGs, but the impact on IDH1 mtLGGs requires further study.

Thalamic Glioblastoma: Clinical Presentation, Management Strategies, and Outcomes.

BACKGROUND: Thalamic glioblastomas (GBMs) represent a significant neurosurgical challenge. In view of the low incidence of these tumors, outcome data and management strategies are not well defined. OBJECTIVE: To identify the natural history and factors associated with survival in patients with thalamic glioblastoma. METHODS: A retrospective review of all patients with thalamic glioblastoma over a 10-yr period was performed. Presenting clinical, radiological, and outcome data were collected. Chi-squared and Fisher's exact tests were used to compare clinical characteristics across tumor groups. Cox proportional hazard models were utilized to investigate variables of interest with regard to overall survival. RESULTS: Fifty-seven patients met inclusion criteria, with a median age of 53 and median Karnofsky Performance Scale (KPS) score of 80. The most common presenting symptoms were weakness, confusion, and headache. Hydrocephalus was present in 47% of patients preoperatively. Stereotactic biopsy was performed in 47 cases, and 10 patients underwent craniotomy. The median overall survival was 12.2 mo. Higher KPS, younger age, and cerebrospinal fluid (CSF) diversion were correlated with better overall survival univariately, respectively, while the presence of language deficits at initial presentation was associated with poorer survival. In multivariate analysis, the only significant predictor of survival was presenting KPS. CONCLUSION: The overall survival of patients with thalamic glioblastoma is comparable to unresectable lobar supratentorial GBMs. Younger patients and those with good presenting functional status had improved survival. Midbrain involvement by the tumor is not a negative prognostic factor. Improved therapies are needed, and patients should be considered for early trial involvement and aggressive upfront therapy.

Spinal stereotactic body radiotherapy following intralesional curettage with separation surgery for initial or salvage chordoma treatment.

OBJECTIVE Chordoma is a rare malignant tumor for which en bloc resection with wide margins is advocated as primary treatment. Unfortunately, due to anatomical constraints, en bloc resection to achieve wide or marginal margins is not feasible for many patients as the resulting morbidity would be prohibitive. The objective of this study was to evaluate the efficacy of intralesional curettage and separation surgery followed by spinal stereotactic body radiation therapy (SBRT) in patients with chordomas in the mobile spine. METHODS The authors performed a retrospective chart review of all patients with chordoma in the mobile spine treated from 2004 to 2016. Patients were identified from a prospectively collected database. Initially 22 patients were identified with mobile spine chordomas. With inclusion criteria of cytoreductive separation surgery followed closely by SBRT and a minimum of 6 months of follow-up imaging, 12 patients were included. Clinical and pathological characteristics of each patient were collected and data were analyzed. Patients were divided into two cohorts-those undergoing intralesional resection followed by SBRT as initial chordoma treatment at Memorial Sloan Kettering Cancer Center (MSKCC) (Cohort 1) and those undergoing salvage treatment following recurrence (Cohort 2). Treatment toxicities were classified according to the Common Terminology Criteria for Adverse Events version 4.03. Overall survival was analyzed using Kaplan-Meier analysis. RESULTS The 12 patients had a median post-SBRT follow-up time of 26 months. Cohort 1 had 5 patients with median post-SBRT follow-up time of 65.9 months and local control rate of 80% at last follow-up. Only one patient had disease progression, at 48.2 months following surgery and SBRT. Cohort 2 had 7 patients who had been treated at other institutions prior to undergoing both surgery and SBRT (salvage therapy) at MSKCC. The local control rate was 57.1% and the median follow-up duration was 10.7 months. One patient required repeat irradiation. Major surgery- and radiation-related complications occurred in 18% and 27% of patients, respectively. Epidural spinal cord compression scores were collected for each patient pre- and postoperatively. CONCLUSIONS The combination of surgery and SBRT provides excellent local control following intralesional curettage and separation surgery for chordomas in the mobile spine. Patients who underwent intralesional curettage and spinal SBRT as initial treatment had better disease control than those undergoing salvage therapy. High-dose radiotherapy may offer several biological benefits for tumor control.

Contralateral supraorbital keyhole approach to medial optic nerve lesions: an anatomoclinical study.

OBJECTIVE The authors describe the supraorbital keyhole approach to the contralateral medial optic nerve and tract, both in a series of cadaveric dissections and in 2 patients. They also discuss the indications and contraindications for this procedure. METHODS In 3 cadaver heads, bilateral supraorbital keyhole minicraniotomies were performed to expose the ipsilateral and contralateral optic nerves. The extent of exposure of the medial optic nerve was assessed. In 2 patients, a contralateral supraorbital keyhole approach was used to remove pathology of the contralateral medial optic nerve and tract. RESULTS The supraorbital keyhole craniotomy provided better exposure of the contralateral superomedial nerve than it did of the same portion of the ipsilateral nerve. In both patients gross-total resections of the pathology was achieved. CONCLUSIONS The authors demonstrate the suitability of the contralateral supraorbital keyhole approach for lesions involving the superomedial optic nerve.

Endoscopic endonasal versus open transcranial resection of craniopharyngiomas: a case-matched single-institution analysis.

OBJECTIVE The authors compared clinical and radiological outcomes after resection of midline craniopharyngiomas via an endoscopic endonasal approach (EEA) versus an open transcranial approach (TCA) at a single institution in a series in which the tumors were selected to be equally amenable to gross-total resection (GTR) with either approach. METHODS A single-institution retrospective review of previously untreated adult midline craniopharyngiomas was performed. Lesions were evaluated by 4 neurosurgeons blinded to the actual approach used to identify cases that were equally amenable to GTR using either an EEA or TCA. Radiological and clinical outcome data were assessed. RESULTS Twenty-six cases amenable to either approach were identified, 21 EEA and 5 TCA. Cases involving tumors that were resected via a TCA had a trend toward larger diameter (p = 0.10) but were otherwise equivalent in preoperative clinical and radiological characteristics. GTR was achieved in a greater proportion of cases removed with an EEA than a TCA (90% vs 40%, respectively; p = 0.009). Endoscopic resection was associated with superior visual restoration (63% vs 0%; p < 0.05), a decreased incidence of recurrence (p < 0.001), lower increase in FLAIR signal postoperatively (-0.16 ± 4.6 cm3 vs 14.4 ± 14.0 cm3; p < 0.001), and fewer complications (20% vs 80% of patients; p < 0.001). Significantly more TCA patients suffered postoperative cognitive loss (80% vs 0; p < 0.0001). CONCLUSIONS An EEA is a safe and effective approach to suprasellar craniopharyngiomas amenable to GTR. For this select group of cases, the EEA may provide higher rates of GTR and visual improvement with fewer complications compared with a TCA.

Advanced Imaging for Biopsy Guidance in Primary Brain Tumors.

Accurate glioma sampling is required for diagnosis and establishing eligibility for relevant clinical trials. MR-based perfusion and spectroscopy sequences supplement conventional MR in noninvasively predicting the areas of highest tumor grade for biopsy. We report the case of a patient with gliomatosis cerebri and multifocal patchy enhancement in whom the combination of advanced and conventional imaging attributes successfully guided a diagnostic biopsy.

Five-Year Outcomes of High-Dose Single-Fraction Spinal Stereotactic Radiosurgery.

PURPOSE: To characterize local tumor control and toxicity risk in very long-term survivors (>5 years) after high-dose spinal image guided, intensity modulated radiation therapy delivered as single-dose stereotactic radiosurgery (SRS). Previously published spinal SRS outcome analyses have included a heterogeneous population of cancer patients, mostly with short survival. This is the first study reporting the long-term tumor control and toxicity profiles after high-dose single-fraction spinal SRS. METHODS AND MATERIALS: The study population included all patients treated from June 2004 to July 2009 with single-fraction spinal SRS (dose 24 Gy) who had survived at least 5 years after treatment. The endpoints examined included disease progression, surgical or radiation retreatment, in-field fracture development, and radiation-associated toxicity, scored using the Radiation Therapy Oncology Group radiation morbidity scoring criteria and the Common Terminology Criteria for Adverse Events, version 4.0. Local control and fracture development were assessed using Kaplan-Meier analysis. RESULTS: Of 278 patients, 31 (11.1%), with 36 segments treated for spinal tumors, survived at least 5 years after treatment and were followed up radiographically and clinically for a median of 6.1 years (maximum 102 months). The histopathologic findings for the 5-year survivors included radiation-resistant metastases in 58%, radiation-sensitive metastases in 22%, and primary bone tumors in 19%. In this selected cohort, 3 treatment failures occurred at a median of 48.6 months, including 2 recurrences in the radiation field and 1 patient with demonstrated progression at the treatment margins. Ten lesions (27.8%) were associated with acute grade 1 cutaneous or gastrointestinal toxicity. Delayed toxicity ≥ 3 months after treatment included 8 cases (22.2%) of mild neuropathy, 2 (5.6%) of gastrointestinal discomfort, 8 (22.2%) of dermatitides, and 3 (8.3%) of myalgias/myositis. Thirteen treated levels (36.1%) in 12 patients demonstrated progressive vertebral body collapse or endplate fractures at a median of 25.7 months (range 11.6-76.0), of which 5 (14%) became symptomatic and subsequently required percutaneous cement augmentation or surgery. CONCLUSIONS: In the longest-term series to date, high-dose single-fraction spinal SRS retained an excellent safety profile among long-term survivors (>5 years).

Short-segment percutaneous pedicle screw fixation with cement augmentation for tumor-induced spinal instability.

BACKGROUND CONTEXT: Pathologic vertebral compression fractures (VCFs) represent a major source of morbidity and diminished quality of life in the spinal oncology population. Procedures with low morbidity that effectively treat patients with pathologic fractures are especially important in the cancer population where life expectancy is limited. Vertebroplasty and kyphoplasty are often not effective for mechanically unstable pathologic fractures extending into the pedicle and facet joints. Combination of cement augmentation and percutaneous instrumented stabilization represents a minimally invasive treatment option that does not delay radiation and systemic therapy. PURPOSE: The objective of the study was to evaluate the safety and efficacy of cement-augmented short-segment percutaneous posterolateral instrumentation for tumor-associated VCF with pedicle and joint involvement. METHODS: Forty-four consecutive patients underwent cement-augmented percutaneous spinal fixation for unstable tumors between 2011 and 2014. Retrospective analysis of prospectively collected data, including visual analog pain scale (VAS) response score and procedural complications, was performed. RESULTS: Patients with a median composite Spinal Instability Neoplastic Scale score of 10 (range=8-15) were treated with constructs spanning one to four disk spaces (median of two spaces, constituting 84% of all cases). The proportion of patients with severe pain decreased from 86% preoperatively to 0%; 65% of patients reported no referable instability pain postoperatively. There was one adjacent-level fracture responsive to kyphoplasty, and one case of asymptomatic screw pullout. Two patients subsequently required decompression in the setting of disease progression despite radiation; there was no perioperative morbidity. CONCLUSIONS: Percutaneous cement-augmented posterolateral spinal fixation is a safe and effective option for palliation of appropriately selected mechanically unstable VCF that extends into pedicle and/or joint.

Endoscopic endonasal resection of skull base chondrosarcomas: technique and early results.

OBJECT: The authors of this study sought to report the technique and early clinical outcomes of a purely endonasal endoscopic approach for resection of petroclival chondrosarcomas. METHODS: Between 2010 and 2014, 8 patients (4 men and 4 women) underwent endonasal endoscopic operations to resect petroclival chondrosarcomas at 2 institutions. The patients' mean age was 44.8 years (range 30-64 years). One of the patients had previously undergone radiation therapy and another a staged craniotomy. Using volumetric software, an independent neuroradiologist assessed the extent of the resections on MRI scans taken immediately after surgery and at the 3-month follow-up. Immediate complications and control of symptoms were also recorded. In addition, the authors reviewed the current literature on surgical treatment of chondrosarcoma. RESULTS: The mean preoperative tumor diameter and volume were 3.4 cm and 9.8 cm(3), respectively. Six patients presented with cranial neuropathies. Endonasal endoscopic surgery achieved > 95% resection in 5 of the 8 patients and < 95% resection in the remaining 3 patients. One of the 6 neuropathies resolved, and the remaining 5 partially improved. One instance of postoperative CSF leakage required a reoperation for repair; no other complications associated with these operations were observed. All of the patients underwent adjuvant radiotherapy. CONCLUSIONS: According to the authors' experience, the endoscopic endonasal route is a safe and effective approach for the resection of appropriately selected petroclival chondrosarcomas.

Sacroplasty for cancer-associated insufficiency fractures.

BACKGROUND: Tumor-associated sacral insufficiency fractures (SIF) present a significant clinical challenge. As survival increases for many malignancies, sacral fractures associated with metastases, sacral or extended pelvic radiation, and paraneoplastic osteoporosis are increasingly common and yet remain difficult to treat in the setting of the potentially significant morbidity of open sacral surgery. OBJECTIVE: To describe our prospective experience with sacroplasty for tumor-associated lesions, including the largest series to date of radiation-induced SIF. METHODS: Twenty-five patients with symptomatic SIF underwent 31 percutaneous fluoroscopy-guided sacroplasties with a median 5.8 mL of polymethyl methacrylate or a ceramic-resin composite under fluoroscopic guidance and with concurrent biopsy acquisition. Eighteen patients had fractures related to previous sacral or pelvic radiation; 4 had viable lytic lesions; and 2 had oncology-related osteoporosis. Postoperative pain reduction, procedural morbidity, and functional outcomes were recorded. RESULTS: Twenty of 25 patients (80%) had reduction in their visual analog pain score at a median follow-up of 6.5 months; no patients worsened. The mean visual analog scale score decreased from 8.8 to 4.7 postprocedurally (P < .001), with significant reductions regardless of the underlying pathology (P < .001 to P < .05). Six of 13 patients with pretreatment ambulatory impairment required fewer ambulatory aids and 3 were newly ambulatory. Extravertebral cement migration was noted in 18 procedures; however, no instance was clinically relevant. Six repeat or contralateral procedures were performed. No morbidity was encountered. CONCLUSION: Sacroplasty is a safe and effective option for the palliation of sacral fractures in the oncologic population.

Separation surgery for spinal metastases: effect of spinal radiosurgery on surgical treatment goals.

BACKGROUND: The treatment of epidural spinal cord compression due to metastatic cancer represents an important clinical challenge. The NOMS (neurologic, oncologic, mechanical, and systemic) framework facilitates the determination of the optimal combination of systemic, radiation, and surgical therapies for individual patients. Spinal stereotactic radiosurgery (SRS) is an effective and safe modality for achieving durable control of local disease. Integrating SRS into the postoperative treatment plan allows surgical goals to be modified, thus decreasing the extent of tumor resection required. METHODS: Separation surgery is indicated for patients with spinal cord compression secondary to solid tumor metastases. During separation surgery, the spinal column is stabilized and the epidural tumor is resected without requiring significant vertebral body resection. RESULTS: Tumor separation from the spinal cord allows patients to undergo postoperative SRS. CONCLUSIONS: The combination of separation surgery and high-dose hypofractionated or single-fraction SRS results in high local tumor control at 1 year and is an effective palliative paradigm for this patient population.

Case-specific protocol to reduce cerebrospinal fluid leakage after endonasal endoscopic surgery.

OBJECT: Endoscopic transsphenoidal surgery is expanding in acceptance, yet postoperative CSF leak rates remain a concern. This study presents the Cornell closure protocol, which has yielded significantly lower postoperative CSF leak rates compared with prior reports, as an algorithm that can be used by centers having difficulty with CSF leak. METHODS: A single closure algorithm for endoscopic surgery has been used since January 2010 at Weill Cornell Medical College. A prospective database noting intraoperative CSF leak, closure technique, and postoperative CSF leak was reviewed. The authors used a MEDLINE search to identify similar studies and compared CSF leak rates to those of patients treated using the Cornell algorithm. RESULTS: The retrospective study of a prospectively acquired database included 209 consecutive patients. In 84 patients (40%) there was no intraoperative CSF leak and no postoperative CSF leak. In the 125 patients (60%) with an intraoperative CSF leak, 35 of them with high-flow leaks, there were 0 (0%) postoperative CSF leaks. CONCLUSIONS: It is possible to achieve a CSF leak rate of 0% by using this closure protocol. With proper experience, endoscopic skull base surgery should not be considered to have a higher CSF leak rate than open transcranial or microscopic transsphenoidal surgery.

Efficacy of vagus nerve stimulation in brain tumor-associated intractable epilepsy and the importance of tumor stability.

OBJECT: Vagus nerve stimulation (VNS) is a viable option for patients with medically intractable epilepsy. However, there are no studies examining its effect on individuals with brain tumor-associated intractable epilepsy. This study aims to evaluate the efficacy of VNS in patients with brain tumor-associated medically intractable epilepsy. METHODS: Epilepsy surgery databases at 2 separate epilepsy centers were reviewed to identify patients in whom a VNS device was placed for tumor-related intractable epilepsy between January 1999 and December 2011. Preoperative and postoperative seizure frequency and type as well as antiepileptic drug (AED) regimens and degree of tumor progression were evaluated. Statistical analysis was performed using odds ratios and t-tests to examine efficacy. RESULTS: Sixteen patients were included in the study. Eight patients (50%) had an improved outcome (Engel Class I, II, or III) with an average follow-up of 39.6 months. The mean reduction in seizure frequency was 41.7% (p = 0.002). There was no significant change in AED regimens. Seizure frequency decreased by 10.9% in patients with progressing tumors and by 65.6% in patients with stable tumors (p = 0.008). CONCLUSIONS: Vagus nerve stimulation therapy in individuals with brain tumor-associated medically intractable epilepsy was shown to be comparably effective in regard to seizure reduction and response rates to the general population of VNS therapy patients. Outcomes were better in patients with stable as opposed to progressing tumors. The authors' findings support the recommendation of VNS therapy in patients with brain tumor-associated intractable epilepsy, especially in cases in which imminent tumor progression is not expected. Vagus nerve stimulation may not be indicated in more malignant tumors.

Encapsulated pheochromocytoma cells secrete potent noncatecholamine factors.

Pheochromocytomas are widely believed to induce cardiomyopathy via hypersecretion of catecholamines, including norepinephrine (NE). NE can have direct cardiomyocyte toxicity and/or can stimulate myocardial remodeling secondary to the induction of hypertension. Yet, the development of cardiomyopathy is not entirely related to catecholamine dose or the extent of hypertension. To explore these effects, we engineered a polymeric encapsulation system to control PC12 cell kinetics and NE release in vitro and in vivo. Primary neonatal rat cardiomyocytes incubated with pheochromocytoma-conditioned media exhibited greater cytoskeletal changes than myocytes cultured with identical doses of NE alone, including more profound dose-dependent decreases in desmin, beta-tubulin, and vinculin and upregulation of dystrophin. Cardiomyocyte contractility was 29 +/- 6% greater at given levels of NE release. Agarose-encapsulated PC12 cells retain cell viability and structural integrity in vivo. These implants induce a 30% greater degree of cardiac enlargement as compared to pumps releasing equivalent doses of NE. Protein level alterations observed in vitro were mirrored in vivo after implantation of encapsulated cells or NE pumps for 28 days. Together, these data suggest that pheochromocytoma-induced cardiomyopathy is not solely a catecholamine-mediated event; rather, the pathogenesis of this dilated cardiomyopathy appears to be dependent upon secondary factors unexamined to date.

Cytokine preconditioning promotes codifferentiation of human fetal liver CD133+ stem cells into angiomyogenic tissue.

BACKGROUND: CD133 (AC133) is a surface antigen that defines a broad population of stem cells, including myogenic and endothelial progenitors. CD133+ cells are rare in adult tissues, and the factors that support their differentiation into mature angiomyogenic cells are not known. These hurdles have hampered the use of CD133+ cells for therapeutic purposes. Because human fetal liver is a rich source of CD133+ cells, we sought to identify the growth factors that promote codifferentiation of these cells into angiogenic and myogenic cells. METHODS AND RESULTS: Human fetal liver CD133+ and CD133- cell subpopulations were cultured with 5'-azacytidine or vascular endothelial growth factor (VEGF165) and/or brain-derived nerve growth factor (BDNF). CD133+ but not CD133- cells from human fetal liver codifferentiated into spindle-shaped cells, as well as flat adherent multinucleated cells capable of spontaneous contractions in culture. The resulting spindle-shaped cells were confirmed to be endothelial cells by immunohistochemistry analysis for von Willebrand factor and by acetylated LDL uptake. Multinucleated cells were characterized as striated muscles by electron microscopy and immunohistochemistry analysis for myosin heavy chain. Presence of VEGF165 and BDNF significantly enhanced angiomyogenesis in vitro. Inoculation of cells derived from CD133+ cells, but not CD133- cells, into the ear pinna of NOD/SCID mice resulted in the formation of cardiomyocytes, as identified by immunostaining with cardiac troponin-T antibody. These cells generated electrical action potentials, detectable by ECG tracing. CONCLUSIONS: CD133 defines a population of human fetal liver cells capable of differentiating into both angiogenic and myogenic cells. Preconditioning of these CD133+ cells with VEGF165 and BDNF enhances the angiomyogenesis. CD133+ fetal liver cells ultimately may be used for therapeutic angiomyogenesis.